Original Article Neuroprotective effect of A2AR knockout on cerebral ischemia/reperfusion injury via the inhibition of microglia activation

The present study was designed to investigate the neuroprotective effects of A2AR inhibition in stroke and to elucidate the mechanisms. Focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 30 min in mild mice and A2AR knockout mice followed by 1 d, 3 d, and 7 d reperfusion. The neurobehavioral scores and the activities of microglia were evaluated after MCAO. We found that A2AR knockout inhibiting microglial activa- tion. But there was no significantly difference of neurobehavioral scores between wild type and A2AR knockout mice in every time point. Perhaps it related with few sample size. To further seek the mechanism, we checked the effects of A2AR blockade on the TNF-a expression in the primary microglia in an oxygen-glucose deprivation/reperfusion (OGD/R) condition. In vitro data showed that A2AR blockade decreased the TNF-a expression. A2AR knockout might improve neurological functional deficits in mice with cerebral ischemia/reperfusion (I/R) injury in which may relate with inhibition of microglia activation and with reducing inflammatory cytokines expression in brain.